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Low-dose photon irradiation induces invasiveness through the SDF-1α/CXCR4 pathway in malignant mesothelioma cells
Yoshikane Yamauchi1, Seyer Safi1, Lena Orschiedt2,3
1Department of Thoracic Surgery, Thorax Clinic, Heidelberg University, Heidelberg, Germany.
Background:
Low-dose photon irradiation has repeatedly been suspected to increase a risk of promoting local recurrence of disease or even systemic dissemination. The purpose of this study was to investigate the motility of malignant pleural mesothelioma (MPM) cell lines after low-doses of photon irradiation and to elucidate the mechanism of the detected phenotype.
Methods:
H28 and H226 MPM cells were examined in clonogenic survival experiments and migration assays with and without various doses of photon and carbon ion irradiation. C-X-C chemokine receptor type 4 (CXCR4), SDF-1α, β1 integrin, α3 integrin, and α5 integrin expressions were analyzed by quantitative FACS analysis, ELISA and western blots. Apoptosis was assessed via Annexin-V-staining.
Results:
The migration of MPM cells was stimulated by both fetal bovine serum and by stromal cell-derived factor 1α (SDF-1α). Low doses of photon irradiation (1 Gy and 2 Gy) suppressed clonogenicity, but promoted migration of both H28 and H226 cells through the SDF-1α/CXCR4 pathway. Hypermigration was inhibited by the administration of CXCR4 antagonist, AMD3100. In contrast, corresponding doses of carbon ion irradiation (0.3 Gy and 1 Gy) suppressed clonogenicity, but did not promote MPM cell migration.
Conclusion:
Our findings suggest that the co-administration of photon irradiation and the CXCR4-antagonist AMD3100 or the use of carbon ions instead of photons may be possible solutions to reduce the risk of locoregional tumor recurrence after radiotherapy for MPM.
Insights
Low-dose photon radiation increases malignant pleural mesothelioma cell migration via the SDF-1α/CXCR4 pathway. Carbon ions did not promote migration, suggesting alternative radiotherapy strategies to reduce recurrence risk.
Area of Science:
- Oncology
- Radiotherapy
- Cell Biology
Background:
- Low-dose photon irradiation is suspected to increase local recurrence and systemic dissemination risks.
- Malignant pleural mesothelioma (MPM) is a challenging cancer with limited treatment options.
Purpose of the Study:
- To investigate the effect of low-dose photon irradiation on MPM cell motility.
- To elucidate the underlying molecular mechanisms of radiation-induced changes in MPM cell behavior.
Main Methods:
- Clonogenic survival and migration assays were performed on MPM cell lines (H28, H226).
- Cells were exposed to photon and carbon ion irradiation at various doses.
- Expression of CXCR4, SDF-1α, and integrins was analyzed using FACS, ELISA, and Western blot.
- Apoptosis was assessed via Annexin-V staining.
Main Results:
- Low-dose photon irradiation (1-2 Gy) suppressed clonogenicity but promoted MPM cell migration.
- MPM cell migration was enhanced via the stromal cell-derived factor 1α (SDF-1α)/C-X-C chemokine receptor type 4 (CXCR4) pathway.
- The CXCR4 antagonist AMD3100 inhibited photon irradiation-induced hypermigration.
- Carbon ion irradiation (0.3-1 Gy) suppressed clonogenicity without promoting migration.
Conclusions:
- Photon irradiation at low doses can enhance MPM cell migration through the SDF-1α/CXCR4 pathway.
- Carbon ion irradiation may offer a safer alternative by not promoting cell migration.
- Co-administration of photon irradiation with CXCR4 antagonists or using carbon ions could reduce locoregional recurrence risk in MPM radiotherapy.
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